Randomized phase II trial of budesonide versus placebo in high-risk population with screening-detected lung nodules: Update on secondary endpoints

Abstract

1518 Background: Lung cancer phase II chemoprevention trials have not focused so far on the peripheral lung. CT discovers small, undetermined peripheral nodules, which may be preinvasive lesions. In a recent phase II trial the glucocorticoid Budesonide reduced peripheral nodules at spiral CT. Methods: We performed a randomized, double-blind, placebo-controlled, phase IIb clinical trial of inhaled budesonide in current (CS) or former smokers (FS) with CT-detected peripheral nodules. Primary endpoint: shrinkage effect on nodules. Secondary endpoints: decrease in size/number of the target lesions, modulation of tumor markers in sputum and plasma, toxicity, effect on pulmonary function. Two hundred and two subjects received 800μg budesonide (B) twice daily or placebo (P) for 1 year. CT scans at 0 and 12 months (mts), and clinical evaluation + serum/plasma collection at 0, 3, 6, and 12 months were performed. Subjects were stratified according to gender, smoking habits (CS vs. FS), and nodule characteristics (solid vs. non-solid). Results: Preliminary data had shown no shrinkage of the nodules in the B treated arm in a per subject analysis (primary objective). We present now results on serum markers (ultrasensitive C-reactive protein, CRP), emphysema and pulmonary function. As compared to baseline, CRP median levels show at 12 months a nonsignificant (p = 0.85) reduction: -0.25 ± 0.63 (B) vs. -1.16 ± 0.97 (P). 12-month values are significantly (p = 0.01) associated with baseline values and smoking status, with higher mean values at 12 months in FS (B 2.1 ± 2.0 vs. P 3.4 ± 1.9). Emphysema values at 12 months are significantly higher (p = 0.0022) in the B (+ 0.29 ± 0.06) versus P arm (+ 0.12 ± 0.07). This difference is not correlated to sex (p = 0.7062) and smoking status (p = 0.8044). As regards spirometry, no significant difference on FEV 1% and DLC/VA appears between arms at 12 months: median FEV 1% values 3.7 ± 1.0 for B versus 2.9 ± 1.0 for P (p = 0.6221); median DLC/VA increase of 0.3 ± 1.9 (B) versus decrease of -3.8 ± 1.6 (P) (p = 0.4191). Conclusions: A significant effect of B on ultrasensitive-CRP and pulmonary function has not been shown. CRP results may indicate the lack of systemic absorption of B. Emphysema appears slightly worse in the B arm, particularly in FS; this is worth further investigation. No significant financial relationships to disclose.